Glycosylation Biomarkers Associated with Age-Related Diseases and Current Methods for Glycan Analysis

Ageing is a complex process which implies the accumulation of molecular, cellular and organ damage, leading to an increased vulnerability to disease. In Western societies, the increase in the elderly population, which is accompanied by ageing-associated pathologies such as cardiovascular and mental diseases, is becoming an increasing economic and social burden for governments. In order to prevent, treat and determine which subjects are more likely to develop these age-related diseases, predictive biomarkers are required. In this sense, some studies suggest that glycans have a potential role as disease biomarkers, as they modify the functions of proteins and take part in intra- and intercellular biological processes. As the glycome reflects the real-time status of these interactions, its characterisation can provide potential diagnostic and prognostic biomarkers for multifactorial diseases. This review gathers the alterations in protein glycosylation profiles that are associated with ageing and age-related diseases, such as cancer, type 2 diabetes mellitus, metabolic syndrome and several chronic inflammatory diseases. Furthermore, the review includes the available techniques for the determination and characterisation of glycans, such as liquid chromatography, electrophoresis, nuclear magnetic resonance and mass spectrometry.

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Age-related exacerbation of hematopoietic organ damage induced by systemic hyper-inflammation in senescence-accelerated mice

Scientific Reports ◽

10.1038/s41598-021-02621-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tomonori Harada ◽

Isao Tsuboi ◽

Hirotsugu Hino ◽

Miyuki Yuda ◽

Yoko Hirabayashi ◽

...

Keyword(s):

Stromal Cells ◽

The Elderly ◽

Organ Damage ◽

Hematopoietic Organ ◽

Aged Mice ◽

Gm Csf ◽

Expression Of Genes ◽

Age Related ◽

Genes Encoding ◽

Positive Regulators

AbstractHemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyper-inflammatory disorder. The mortality of HLH is higher in the elderly than in young adults. Senescence-accelerated mice (SAMP1/TA-1) exhibit characteristic accelerated aging after 30 weeks of age, and HLH-like features, including hematopoietic organ damage, are seen after lipopolysaccharide (LPS) treatment. Thus, SAMP1/TA-1 is a useful model of hematological pathophysiology in the elderly with HLH. In this study, dosing of SAMP1/TA-1 mice with LPS revealed that the suppression of myelopoiesis and B-lymphopoiesis was more severe in aged mice than in young mice. The bone marrow (BM) expression of genes encoding positive regulators of myelopoiesis (G-CSF, GM-CSF, and IL-6) and of those encoding negative regulators of B cell lymphopoiesis (TNF-α) increased in both groups, while the expression of genes encoding positive-regulators of B cell lymphopoiesis (IL-7, SDF-1, and SCF) decreased. The expression of the GM-CSF-encoding transcript was lower in aged mice than in young animals. The production of GM-CSF by cultured stromal cells after LPS treatment was also lower in aged mice than in young mice. The accumulation of the TNF-α-encoding transcript and the depletion of the IL-7-encoding transcript were prolonged in aged mice compared to young animals. LPS dosing led to a prolonged increase in the proportion of BM M1 macrophages in aged mice compared to young animals. The expression of the gene encoding p16INK4a and the proportion of β-galactosidase- and phosphorylated ribosomal protein S6-positive cells were increased in cultured stromal cells from aged mice compared to those from young animals, while the proportion of Ki67-positive cells was decreased in stromal cells from aged mice. Thus, age-related deterioration of stromal cells probably causes the suppression of hematopoiesis in aged mice. This age-related latent organ dysfunction may be exacerbated in elderly people with HLH, resulting in poor prognosis.

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HIV infection and aging of the innate immune system

Sexual Health ◽

10.1071/sh11028 ◽

2011 ◽

Vol 8 (4) ◽

pp. 453 ◽

Cited By ~ 20

Author(s):

Anna C. Hearps ◽

Thomas A. Angelovich ◽

Anthony Jaworowski ◽

John Mills ◽

Alan L. Landay ◽

...

Keyword(s):

Immune System ◽

Hiv Infection ◽

Immune Cells ◽

Inflammatory Diseases ◽

The Elderly ◽

Innate Immune ◽

Innate Immune Cells ◽

Telomere Attrition ◽

Age Related ◽

The Impact

The increased life expectancy of HIV-infected individuals due to improved treatment has revealed an unexpected increase in non-AIDS comorbidities that are typically associated with older age including cardiovascular disease, dementia and frailty. The majority of these diseases arise as the result of dysregulated systemic inflammation, and both the aged and HIV-infected individuals exhibit elevated basal levels of inflammation. In the elderly, increased inflammation and age-related diseases are associated with a state of impaired immunity called immunosenescence, which is thought to result from a lifetime of immune stimulation. It is now apparent that HIV induces premature immunosenescence within T-cells; however, the impact of HIV on aging of cells of the innate arm of the immune system is unknown. Innate immune cells play a central role in inflammation and are thus critical for the pathogenesis of inflammatory diseases. Limited evidence suggests HIV infection mimics age-related changes to innate immune cells; however, the extent of this effect and the mechanism underlying these changes remain to be defined. This review focuses on the impact of HIV infection on the function and aging of innate immune cells and discusses potential drivers of premature immunosenescence including chronic endotoxaemia, residual viraemia, telomere attrition and altered cellular signalling.

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Ageing and the border between health and disease

European Respiratory Journal ◽

10.1183/09031936.00134014 ◽

2014 ◽

Vol 44 (5) ◽

pp. 1332-1352 ◽

Cited By ~ 45

Author(s):

William MacNee ◽

Roberto A. Rabinovich ◽

Gourab Choudhury

Keyword(s):

Negative Impact ◽

Inflammatory Diseases ◽

The Elderly ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Progressive Degeneration ◽

Age Related ◽

Chronic Pulmonary Diseases ◽

Health And Disease ◽

And Function

Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world’s population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources.There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations.

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Age-related changes in immunity: implications for vaccination in the elderly

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399407000221 ◽

2007 ◽

Vol 9 (3) ◽

pp. 1-17 ◽

Cited By ~ 92

Author(s):

Rania D. Kovaiou ◽

Dietmar Herndler-Brandstetter ◽

Beatrix Grubeck-Loebenstein

Keyword(s):

The Elderly ◽

Developed Countries ◽

Cellular Level ◽

The Body ◽

Strong Impact ◽

Antigen Delivery ◽

Average Life Expectancy ◽

Age Related ◽

Complex Process ◽

The Many

Average life expectancy is continuously rising in all developed countries, leading to an ever-increasing elderly population. Of the many functions of the body affected by the complex process of ageing, the immune system in particular undergoes various changes, collectively termed immunosenescence. As a result, elderly people are more susceptible to infections and are frequently less protected by vaccines. This review summarises the effect of ageing on immunity, emphasising the age-associated changes within T and B cells at a molecular and cellular level. Furthermore, it discusses strategies, such as the addition of immunostimulatory adjuvants and the use of potent antigen-delivery systems, that may counteract age-related defects in immune responses to vaccination. A proper understanding of how immunological memory is affected by ageing, and the introduction of strategies to ameliorate vaccine efficacy in the elderly, might reduce the incidence and the severity of infectious disease within this fragile age group and have a strong impact on the quality of life of elderly individuals.

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Tumorigenic Aspects of MSC Senescence—Implication in Cancer Development and Therapy

Journal of Personalized Medicine ◽

10.3390/jpm11111133 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1133

Author(s):

Slavko Mojsilović ◽

Aleksandra Jauković ◽

Tamara Kukolj ◽

Hristina Obradović ◽

Ivana Okić Đorđević ◽

...

Keyword(s):

Inflammatory Diseases ◽

Tumor Development ◽

The Elderly ◽

Low Grade ◽

Innate And Adaptive Immunity ◽

Physiological Processes ◽

Age Related ◽

Tumor Prevention ◽

Stromal Stem Cells

As an organism ages, many physiological processes change, including the immune system. This process, called immunosenescence, characterized by abnormal activation and imbalance of innate and adaptive immunity, leads to a state of chronic low-grade systemic inflammation, termed inflammaging. Aging and inflammaging are considered to be the root of many diseases of the elderly, as infections, autoimmune and chronic inflammatory diseases, degenerative diseases, and cancer. The role of mesenchymal stromal/stem cells (MSCs) in the inflammaging process and the age-related diseases is not completely established, although numerous features of aging MSCs, including altered immunomodulatory properties, impeded MSC niche supporting functions, and senescent MSC secretory repertoire are consistent with inflammaging development. Although senescence has its physiological function and can represent a mechanism of tumor prevention, in most cases it eventually transforms into a deleterious (para-)inflammatory process that promotes tumor growth. In this review we are going through current literature, trying to explore the role of senescent MSCs in making and/or sustaining a microenvironment permissive to tumor development and to analyze the therapeutic options that could target this process.

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Novel delivery systems of active substances for intraocular administration

Anales de la Real Academia Nacional de Farmacia ◽

10.53519/analesranf.2021.87.03.08 ◽

2021 ◽

Vol 87 (87(03)) ◽

pp. 331-338

Author(s):

Rocío Herrero Vanrell

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

The Elderly ◽

Delivery Systems ◽

Posterior Segment ◽

Age Related Macular Degeneration ◽

Multifactorial Diseases ◽

Age Related ◽

Intraocular Drug Delivery ◽

Active Substances

Neurodegenerative pathologies affecting the posterior segment of the eye such as diabetic retinopathy, age related macular degeneration and glaucoma are among the main causes of blindness in the world. They have in common that are cronic, multifactorial and in some cases related with the elderly. The treatment of these pathologies require to maintain therapeutic concentrations in the posterior segment thanks to the use of successive intraocular injections which are associated to secondary effects being poor tolerated by patients. Intraocular drug delivery systems emerged as an alternative to frequent injections as they are able to deliver the therapeutic agent in a controlled fashion into the eye after a single administration. Depending on the biomaterial these delivery systems are biodegradable or non biodegradable. Attending to their sizes, drug delivery systems are classified in implants (>1mm), microsystems (1-1000μm) y nanosystems (1-1000nm). Biodegradable microspheres emerge as therapeutic tools of great interest for the treatment of neurodegenerative pathologies as they can encapsulate active substances of distinct nature and provide release profiles tailoring with clinical needs. Furthermore, it is possible to administer different amounts of microspheres which correspond to the most adequated doses of the medicine in a personalized therapy. The simultaneous encapsulation of several active substances in the microspheres are of great interest in the treatment of multifactorial diseases covering different therapeutic targets.

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Effects of age on antibody affinity maturation

Biochemical Society Transactions ◽

10.1042/bst0310447 ◽

2003 ◽

Vol 31 (2) ◽

pp. 447-448 ◽

Cited By ~ 39

Author(s):

D.K. Dunn-Walters ◽

M. Banerjee ◽

R. Mehr

Keyword(s):

Inflammatory Diseases ◽

The Elderly ◽

Affinity Maturation ◽

Antibody Affinity ◽

Mortality And Morbidity ◽

Humoral Immune ◽

Selection Processes ◽

Age Related ◽

Actual Mechanism ◽

Patient Groups

The elderly are more susceptible to infectious diseases. Mortality and morbidity from infections increase sharply over the age of 65 years. At the same time, the efficacy of vaccinations in the elderly is decreased. The elderly also have an increased incidence of cancer and inflammatory diseases. All the above indicate an age-related dysregulation of the immune system. Evidence suggests that the change in the humoral immune response with age is a qualitative rather than a quantitative one, i.e. it is the affinity and specificity of the antibody that changes, rather than the quantity of antibody produced. There are a number of possible causes of this failure, one of which is a defect in the mechanism of hypermutation of immunoglobulin genes. We have studied individual clonal responses within germinal centres of spleen and Peyer's patches in young and old patient groups. Our results indicate that there is no difference in the actual mechanism of hypermutation with age. There are, however, differences that are due either to a change in selection processes or to a change in the founder cells available for activation.

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The Biological Clock and Sleep in the Elderly

Zeitschrift für Gerontopsychologie & -psychiatrie ◽

10.1024/1011-6877.19.1.45 ◽

2006 ◽

Vol 19 (1) ◽

pp. 45-51 ◽

Cited By ~ 1

Author(s):

Myriam Juda ◽

Mirjam Münch ◽

Anna Wirz-Justice ◽

Martha Merrow ◽

Till Roenneberg

Keyword(s):

Circadian Rhythms ◽

Biological Clock ◽

The Elderly ◽

Early Morning ◽

Behavioral Changes ◽

Older Age ◽

Age Related ◽

Theoretical Considerations ◽

Sleep Difficulties ◽

Circadian Biology

Abstract: Among many other changes, older age is characterized by advanced sleep-wake cycles, changes in the amplitude of various circadian rhythms, as well as reduced entrainment to zeitgebers. These features reveal themselves through early morning awakenings, sleep difficulties at night, and a re-emergence of daytime napping. This review summarizes the observations concerning the biological clock and sleep in the elderly and discusses the documented and theoretical considerations behind these age-related behavioral changes, especially with respect to circadian biology.

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What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature

Current Pharmaceutical Design ◽

10.2174/1381612825666190705185033 ◽

2019 ◽

Vol 25 (28) ◽

pp. 3005-3010

Author(s):

Georges Samouri ◽

Alexandre Stouffs ◽

Lionel V. Essen ◽

Olivier Simonet ◽

Marc De Kock ◽

...

Keyword(s):

Frail Elderly ◽

Muscle Fibers ◽

Motor Units ◽

The Elderly ◽

Hepatic Function ◽

Volume Of Distribution ◽

Neuromuscular Blocking ◽

Cancer Surgery ◽

Old People ◽

Age Related

Introduction: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. Method: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. Results: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. : Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. : No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. Conclusion: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

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A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽

10.3390/nu13010183 ◽

2021 ◽

Vol 13 (1) ◽

pp. 183

Author(s):

Anna Izzo ◽

Elena Massimino ◽

Gabriele Riccardi ◽

Giuseppe Della Pepa

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Elderly Population ◽

The Elderly ◽

Narrative Review ◽

Macrovascular Complications ◽

Diabetic Patients ◽

Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

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